27,014 research outputs found
An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes
No full textObjectives The Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale) is the most widely used clinical measure of lithium response phenotypes. We assess its performance against recommended psychometric and clinimetric standards. Methods We used data from the Consortium for Lithium Genetics and a French study of lithium response phenotypes (combined sample >2500) to assess reproducibility, responsiveness, validity, and interpretability of the A scale (assessing change in illness activity), the B scale, and its items (assessing confounders of response) and the previously established response categories derived from the Total Score for the Alda scale. Results The key findings are that the B scale is vulnerable to error measurement. For example, some items contribute little to overall performance of the Alda scale (eg, B2) and that the B scale does not reliably assess a single construct (uncertainty in response). Machine learning models indicate that it may be more useful to employ an algorithm for combining the ratings of individual B items in a sequence that clarifies the noise to signal ratio instead of using a composite score. Conclusions This study highlights three important topics. First, empirical approaches can help determine which aspects of the performance of any scale can be improved. Second, the B scale of the Alda is best applied as a multidimensional index (identifying several independent confounders of the assessment of response). Third, an integrated science approach to precision psychiatry is vital, otherwise phenotypic misclassifications will undermine the reliability and validity of findings from genetics and biomarker studies
Personalized management of bipolar disorder
No full textBipolar disorder (BD) is one of the most serious psychiatric disorders. The rates of disability, the risk of suicide attempts and their high lethality, as well as frequent and severe psychiatric and medical comorbidities, put it among the major causes of mortality and disability worldwide. At the same time, many patients can do well when treated properly. In this review, we focus on those aspects of the clinical care that offer the potential of individualized approach, in the context of the recent technology driven advances in the comprehension of the neurobiological underpinnings of BD. We first review those clinical and biological factors that can help identifying individuals at high risk of developing BD. Among these are a family history of BD and/or completed suicide, prodromal symptoms (in childhood and/or adolescence) such as anxiety and mood lability, early onset, and poor response to antidepressants. Panels of genetic markers are also being studied to identify subjects at risk for BD. Further, neuroimaging studies have found an increased gray matter density in the right Inferior Frontal Gyrus (rIFG) as a possible risk marker of BD. We then examine clinical factors that influence the initiation, selection and possibly discontinuation of long-term treatment. Lastly, we discuss the risk of side effects in BD, and their relevance for treatment adherence and for treatment monitoring. In summary, we discuss how a personalized approach in BD can be implemented through the identification of specific clinical and molecular predictors. We show that the realization of a personalized management of BD is not only of a theoretical value, but has substantial clinical repercussions, resulting in a significant reduction of the long-term morbidity and mortality associated to BD
Asymmetrical reliability of the Alda score favours a dichotomous representation of lithium responsiveness
No full textThe Alda score is commonly used to quantify lithium responsiveness in bipolar disorder. Most often, this score is dichotomized into “responder” and “non-responder” categories, respectively. This practice is often criticized as inappropriate, since continuous variables are thought to invariably be “more informative” than their dichotomizations. We therefore investigated the degree of informativeness across raw and dichotomized versions of the Alda score, using data from a published study of the scale’s inter-rater reliability (n = 59 raters of 12 standardized vignettes each). After learning a generative model for the relationship between observed and ground truth scores (the latter defined by a consensus rating of the 12 vignettes), we show that the dichotomized scale is more robust to inter-rater disagreement than the raw 0-10 scale. Further theoretical analysis shows that when a measure’s reliability is stronger at one extreme of the continuum—a scenario which has received little-to-no statistical attention, but which likely occurs for the Alda score ≥ 7—dichotomization of a continuous variable may be more informative concerning its ground truth value, particularly in the presence of noise. Our study suggests that research employing the Alda score of lithium responsiveness should continue using the dichotomous definition, particularly when data are sampled across multiple raters.</div
Histograms of ratings for each value of the ground truth Alda score available in the first wave dataset from Manchia et al. [1].
No full textEach histogram represents the distribution of ratings (nr = 59) for a single one of twelve assessment vignettes. The gold standard (“ground truth”) Alda score, obtained by the Halifax consensus sample, is depicted as the title for each histogram. Plots in blue are those for vignettes with gold standard Alda scores less than 7, which would be classified as “non-responders” under the dichotomized setting. Vignettes with gold standard Alda scores ≥ 7 are shown in red, and represent the dichotomized group of lithium responders.</p
Asymmetrical reliability of the Alda score favours a dichotomous representation of lithium responsiveness.
No full textThe Alda score is commonly used to quantify lithium responsiveness in bipolar disorder. Most often, this score is dichotomized into "responder" and "non-responder" categories, respectively. This practice is often criticized as inappropriate, since continuous variables are thought to invariably be "more informative" than their dichotomizations. We therefore investigated the degree of informativeness across raw and dichotomized versions of the Alda score, using data from a published study of the scale's inter-rater reliability (n = 59 raters of 12 standardized vignettes each). After learning a generative model for the relationship between observed and ground truth scores (the latter defined by a consensus rating of the 12 vignettes), we show that the dichotomized scale is more robust to inter-rater disagreement than the raw 0-10 scale. Further theoretical analysis shows that when a measure's reliability is stronger at one extreme of the continuum-a scenario which has received little-to-no statistical attention, but which likely occurs for the Alda score ≥ 7-dichotomization of a continuous variable may be more informative concerning its ground truth value, particularly in the presence of noise. Our study suggests that research employing the Alda score of lithium responsiveness should continue using the dichotomous definition, particularly when data are sampled across multiple raters
Mutual information between gold standard and observed Alda scores in relation to the observation noise (<i>α</i>) and whether the scale is in its raw or dichotomized form (lithium responder [Li(+)] is Alda score ≥ 7; non-responder [Li(-)] is Alda score < 7).
No full textPanels A-C show the inferred joint distributions of the observed (xo for raw, yo for discrete) and gold standard (x* for raw, y* for discrete) values at different levels of observation noise (α ∈ {0, 10, 100}). Panel D plots the mutual information for the raw (red) and discrete (blue) settings of the Alda score across increasing values of α. Recall that here we set ξ = 11/2.</p
Jack Alive / Martin Dead : The Location of the "Author" in Jack London\u27s Martin Eden
No full textThis essay is an attempt to read Martin Eden, Jack Londonʼs autobiographical novel, in terms of the inextricable relationship between the author and the protagonist. Critics have often taken the unbalanced plot and the lack of ironic distance between narrator and character in Martin Eden as the technical weakness of London, but this paper argues that the achievement of this novel owes a great deal to the attachment of London to Martin. The unbalanced structure is a necessary product of the severe struggle of the author to kill his romantic alter ego. // Martin, who aspires to win Ruth Morse, tries to cross class boundaries by making a career of a writer. Even after realizing the emptiness of Ruth, who turns out to be nothing but a typical figure of the bourgeoisie, he somehow persists in loving her. The notion underlying here is that, for Martin, love, career and art are fundamentally inseparable. He objects to the aestheteʼs view of Brissenden on account of his separation of art from career. Martinʼs identity and life consist only in the triunity of love/career/art; the alternative is the repudiation of life. Thus, the unnatural delay of his disappointment in love can be regarded as Londonʼs strategy to set the suicide of Martin as the necessary consequence of the story. // By finishing the story and killing Martin, London finally detaches himself from Martin, reconstructs his self, and, unlike Martin, survives as a professional writer. In this sense, Martin Eden is a story about “writerʼs self-reconstruction.
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Letter from Martin Chizzick
No full textCongratulations to Duane Pearsall for receiving the Enterpreneur of the Year award; note on the letter was written by Pearsall and it mentions that Martin, the author of the letter, died in a airplane accident
Robert Martin Tiffin's Mystery Man Newspaper Articles
No full textAdvertiser-Tribune newspaper clippings featuring a story about Robert Martin (written by Nancy Kleinhenz), a local author from Tiffin (Ohio) who wrote under the pseudonym of Lee Roberts, and two of his short stories. Martin wrote mystery novels in his spare time, creating more than 22 mystery novels. For more information about Robert Martin and a list of books go to http://www.mysteryfile.com/RMartin/JBennett.html
Lithium and bipolar depression
No full textKelly1 has recently disputed the recommendations of several international guidelines on the use of lithium in bipolar depression. In his scrutiny, the author points to three main errors that seem to have affected systematically ten international guidelines, namely the Woozle effect (evidence by citation), reference inflation (inappropriate citation of pivotal, generally old, studies) and belief perseverance (inability to modify evidence‐based recommendations despite the presence of contrary data). We concur with the author that the evidence supporting the effectiveness of lithium in acute bipolar depression, and to a lesser degree also in major depressive episodes, remains inadequate.2, 3 A different matter is, in our opinion, to label guidelines recommendations as inaccurate or biased, even if, as the author stated, no deceptive intentions were present
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